Transcriptional Changes in Radiation-Induced Lung Injury: A Comparative Analysis of Two Radiation Doses for Preclinical Research.

In a recent stereotactic body radiation therapy animal model, radiation pneumonitis and radiation pulmonary fibrosis were observed at around 2 and 6 weeks, respectively. However, the molecular signature of this model remains unclear. This study aimed to examine the molecular characteristics at these two stages using RNA-seq analysis. Transcriptomic profiling revealed distinct transcriptional patterns for each stage. Inflammatory response and immune cell activation were involved in both stages. Cell cycle processes and response to type II interferons were observed during the inflammation stage. Extracellular matrix organization and immunoglobulin production were noted during the fibrosis stage. To investigate the impact of a 10 Gy difference on fibrosis progression, doses of 45, 55, and 65 Gy were tested. A dose of 65 Gy was selected and compared with 75 Gy. The 65 Gy dose induced inflammation and fibrosis as well as the 75 Gy dose, but with reduced lung damage, fewer inflammatory cells, and decreased collagen deposition, particularly during the inflammation stage. Transcriptomic analysis revealed significant overlap, but differences were observed and clarified in Gene Ontology and KEGG pathway analysis, potentially influenced by changes in interferon-gamma-mediated lipid metabolism. This suggests the suitability of 65 Gy for future preclinical basic and pharmaceutical research connected with radiation-induced lung injury.

Prediction and prevention of central nervous system relapse in patients with extranodal natural killer/T-cell lymphoma.

Because non-anthracycline-based chemotherapy with l-asparaginase has improved survival outcomes in patients with extranodal natural killer/T-cell lymphoma (ENKTL), the incidence of central nerve system (CNS) relapse can be different when compared with that in previous reports. In this research, we sought to identify the incidence of and predictors for CNS relapse and to evaluate the necessity of CNS prophylaxis with intermediate-dose methotrexate (ID-MTX). The records of 399 patients in the training cohort and 253 patients in the validation cohort with ENKTL who received non-anthracycline-based chemotherapy were reviewed. Patients were divided into 2 groups according to whether the chemotherapy regimen included ID-MTX above 2 g/m2. A new central nervous system-prognostic index of natural killer (CNS-PINK) model was developed using 1-point powerful predictors of CNS relapse (PINK; hazard ratio [HR], 2.908; P = .030 and extranodal involvement [≥2]; HR, 4.161; P = .001) and was calculated as a sum of scores. The high-risk group of CNS-PINK was defined as 2 points. The cumulative incidence of CNS relapse was different between the CNS-PINK risk groups in the training (P < .001) and validation (P = .038) cohorts. Patients in the high-risk CNS-PINK group who were treated with SMILE or SMILE-like regimens with ID-MTX (S-ID-MTX) displayed a lower incidence rate of CNS relapse than did those who received other regimens without ID-MTX in the training cohort (P = .029). The CNS-PINK was demonstrated its strong predictability of CNS relapse in ENKTL patients. The effectiveness of S-ID-MTX in preventing CNS events in high-risk CNS-PINK patients should be verified in future studies.

Eradication of Helicobacter pylori infection decreases risk for dyslipidemia: A cohort study.

BACKGROUND: Previous studies have suggested a relationship between Helicobacter pylori infection and dyslipidemia; however, large-scale longitudinal studies have not elucidated this association. This study assessed the longitudinal effects of H. pylori infection and eradication on lipid profiles in a large cohort. METHODS: This cohort study included 2,626 adults without dyslipidemia at baseline, who participated in a repeated, regular health-screening examination, which included upper gastrointestinal endoscopy, between January 2009 and December 2018. The primary outcome was incident dyslipidemia at follow-up. RESULTS: During the 10,324 person-years of follow-up, participants with persistent H. pylori infection had a higher incidence rate (130.5 per 1,000 person-years) of dyslipidemia than those whose infections had been successfully controlled (98.1 per 1,000 person-years). In a multivariable model adjusted for age, sex, waist circumference, smoking status, alcohol intake, and education level, the H. pylori eradication group was associated with a lower risk of dyslipidemia than the persistent group (HR, 0.85; 95% CI, 0.77-0.95; p = 0.004). The association persisted after further adjustment for baseline levels of low-density and high-density lipoprotein cholesterol (HR, 0.87; 95% CI, 0.79-0.97; p = 0.014). CONCLUSIONS: H. pylori infection may play a pathophysiologic role in the development of dyslipidemia, whereas H. pylori eradication might decrease the risk of dyslipidemia.

Prognostic significance of sarcopenia in microsatellite-stable gastric cancer patients treated with programmed death-1 inhibitors.

BACKGROUND: Sarcopenia has been underscored as a significant predictor of poor prognosis in cancer patients undergoing immunotherapy with programmed death-1 (PD-1) inhibitors. We aimed to investigate the prognostic significance of computed tomography (CT)-determined sarcopenia in patients with microsatellite-stable (MSS) gastric cancer (GC) treated with PD-1 inhibitors. METHODS: We retrospectively assessed patients with MSS GC who had been treated with PD-1 inhibitors from March 2016 to June 2019. Pre-treatment sarcopenic status was determined by analyzing L3 skeletal muscle index with abdominal CT. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and the differences in survival probability according to sarcopenic status were compared using the log-rank test. Cox proportional hazards regression analyses were performed to identify predictors of PFS and OS. RESULTS: Of 149 patients with MSS GC (mean age, 57.0 ± 12.3 years; 93 men), 79 (53.0%) had sarcopenia. Patients with sarcopenia had significantly shorter PFS than patients without sarcopenia (median, 1.4 months vs. 2.6 months; P = 0.026). Sarcopenia was independently associated with shorter PFS (adjusted hazard ratio [HR], 1.79; 95% confidence interval [CI], 1.10-2.93; P = 0.020). Patients with sarcopenia had shorter OS than patients without sarcopenia (median, 3.6 months vs. 4.9 months; P = 0.052), but sarcopenia itself was not a significant prognostic factor for OS (adjusted HR, 1.01; 95% CI, 0.58-1.75; P = 0.974). CONCLUSIONS: CT-determined sarcopenia is an independent prognostic factor for PFS in patients with MSS GC treated with PD-1 inhibitors.

Prognostication of a 13-immune-related-gene signature in patients with early triple-negative breast cancer.

PURPOSE: We investigated the expression profiles of immune genes in patients with triple-negative breast cancer (TNBC) to identify the prognostic value of immune genes and their clinical implications. METHODS: NanoString nCounter Analysis of 770 immune-related genes was used to measure immune gene expression in patients with TNBC who underwent curative surgery followed by adjuvant chemotherapy at Samsung Medical Center between 2000 and 2004. Statistical analyses were conducted to identify the associations between gene expression and distant recurrence-free survival (DRFS). RESULTS: Of 1189 patients who underwent curative BC surgery, 200 TNBC patients were included and stage was the only clinical factor predictive of DRFS. In terms of immune genes, 155 of 770 genes were associated with DRFS (p < 0.01). Further multivariate analysis revealed that 13 genes, CD1B, CD53, CT45A1, GTF3C1, IL11RA, IL1RN, LRRN3, MAPK1, NEFL, PRKCE, PTPRC, SPACA3 and TNFSF11, were associated with patient prognosis (p < 0.05). The prognostic value of stage and expression levels of 13 immune genes was analyzed and the area under the receiver operating characteristic curve (AUC) was 0.923. Based on the AUC, we divided patients into three genetic risk groups and DRFS rate was significantly different according to genetic risk groups, even in the same stage (p < 0.001). CONCLUSIONS: In this study, a 13-gene expression profile in combination with stage precisely predicted distant recurrence of early TNBC. Therefore, this 13-immune-gene signature could help predict TNBC prognosis and provide guidance for treatment as well as the opportunity to develop new targets for immunotherapy in TNBC patients.

Accuracy of the qSOFA Score and RED Sign in Predicting Critical Care Requirements in Patients with Suspected Infection in the Emergency Department: A Retrospective Observational Study.

Background and objectives: We aimed to compare the accuracy of positive quick sequential organ failure assessment (qSOFA) scores and the RED sign in predicting critical care requirements (CCRs) in patients with suspected infection who presented to the emergency department (ED). Materials and Methods: In this retrospective observational study, we examined adult patients with suspected infection in the ED from June 2018 to September 2018. A positive qSOFA (qSOFA+) was defined as the presence of ≥2 of the following criteria: altered mental status (AMS), systolic blood pressure (SBP) < 100 mmHg, and respiratory rate (RR) ≥ 22 breaths/min. A positive RED sign (RED sign+) was defined as the presence of at least one of the RED sign criteria: AMS, skin mottling, SBP < 90 mmHg, heart rate >130 beats/min, or RR > 30 breaths/min. A qSOFA/RED+ was defined as the presence of qSOFA+ or RED+. We applied these tools twice using the initial values upon ED arrival and all values within 2 h after ED arrival. The accuracy of qSOFA+, RED+, and qSOFA/RED+ in predicting CCR was assessed. Results: Data from 5353 patients with suspected infection were analyzed. The area under the receiver operating characteristic curve (AUC) of RED+ (0.67, 95% confidence interval [CI]: 0.65-0.70) and that of qSOFA/RED+ (0.68, 95% CI: 0.66-0.70, p < 0.01) were higher than the AUC of qSOFA+ (0.59, 95% CI: 0.57-0.60) in predicting CCR on ED arrival. The qSOFA/RED+ within 2 h showed the highest accuracy (AUC 0.72, 95% CI: 0.70-0.75, p < 0.001). Conclusions: The accuracy of the RED sign in predicting CCR in patients with suspected infection who presented at ED was better than that of qSOFA. The combined use of the RED sign and qSOFA (positive qSOFA or RED sign) showed the highest accuracy.

Prevalence of and risk factors for pulmonary complications after curative resection in otherwise healthy elderly patients with early stage lung cancer.

BACKGROUND AND OBJECTIVE: The prevalence of lung cancer has been increasing in healthy elderly patients with preserved pulmonary function and without underlying lung diseases. We aimed to determine the prevalence of and risk factors for postoperative pulmonary complications (PPCs) in healthy elderly patients with non-small cell lung cancer (NSCLC) to select optimal candidates for surgical resection in this subpopulation. METHODS: We included 488 patients older than 70 years with normal spirometry results who underwent curative resection for NSCLC (stage IA-IIB) between 2012 and 2016. RESULTS: The median (interquartile range) age of our cohort was 73 (71-76) years. Fifty-two patients (10.7%) had PPCs. Severe PPCs like acute respiratory distress syndrome, pneumonia, and respiratory failure had prevalences of 3.7, 3.7, and 1.4%, respectively. Compared to patients without PPCs, those with PPCs were more likely to be male and current smokers; have a lower body mass index (BMI), higher American Society of Anesthesiologists (ASA) classification, more interstitial lung abnormalities (ILAs), and higher emphysema index on computed tomography (CT); and have undergone pneumonectomy or bilobectomy (all p < 0.05). On multivariate analysis, ASA classification ≥3, lower BMI, ILA, and extent of resection were independently associated with PPC risk. The short-term all-cause mortality was significantly higher in patients with PPCs. CONCLUSIONS: Curative resection for NSCLC in healthy elderly patients appeared feasible with 10% PPCs. ASA classification ≥3, lower BMI, presence of ILA on CT, and larger extent of resection are predictors of PPC development, which guide treatment decision-making in these patients.

Pathway genes and metabolites in thiopurine therapy in Korean children with acute lymphoblastic leukaemia.

AIMS: We aimed to investigate the impact of various genetic polymorphisms affecting thiopurine metabolism pathways and toxicity in paediatric acute lymphoblastic leukaemia patients for the first time in Korea. METHODS: From May 2006 to September 2016, 139 paediatric acute lymphoblastic leukaemia patients treated with combination chemotherapy including 6-mercaptopurine were included in the study. One hundred and twenty-three variants in 43 genes, including TMPT and NUDT15, were screened using targeted genotyping, such as a MassARRAY system, direct sequencing and polymerase chain reaction-restriction fragment length polymorphism methods. Among the polymorphisms screened, 103 polymorphisms of 43 genes were included for further analyses. RESULTS: The genetic polymorphisms in the ABCC4, AHCY, ATIC, FAM8A6P, GART, GNG2, GSTA1, MTHFD1, MTHFR, NUDT15, PACSIN2, TYMS and XDH genes, and an intronic polymorphism between HIVEP2 and AIG1, and TPMT genotype were associated with thiopurine metabolism (P < 0.05). Genetic polymorphisms in the ABCC4, ADK, ATIC, GART, GMPS, GSTP1, IMPDH1, ITPA, KCNMA1, MOCOS, MTRR, NUDT15, SLC19A1, SLC28A3, SLC29A1, SLCO1B1, TYMP and XDH genes were associated with thiopurine-related toxicities; neutropenia, hepatotoxicity and treatment interruption (P < 0.05). CONCLUSIONS: Findings of this study may provide basic knowledge for personalized medicine for thiopurinxe treatment in paediatric acute lymphoblastic leukaemia patients.

Risk of high-grade malignancy in parotid gland tumors as classified by the Milan System for Reporting Salivary Gland Cytopathology.

BACKGROUND: The Milan System for Reporting Salivary Gland Cytopathology (Milan System) has previously shown its diagnostic utility by categorizing the seven cytology findings in salivary gland lesions. However, there has been lack of study about the risk of high-grade malignancy in the cytology diagnosis based on the Milan System. Thus, we tried to identify the diagnostic ability of the Milan System for high-grade malignancy and to suggest an improved diagnostic approach for preoperative estimation of high-grade malignancy using the Milan System. METHODS: A total of 413 patients with parotid gland tumors, who had undergone surgical resection from 2011 to 2015 were included in the present study retrospectively. Cytopathology was reclassified according to the Milan System by two independent reviewers. The outcomes were risk of malignancy and risk of high-grade malignancy. The diagnostic performance of the Milan System category [Malignant] for detecting high-grade malignancy was calculated. RESULTS: The risk of malignancy was 83.3% and 100% in the Milan System categories [Suspicious for Malignancy] and [Malignant], respectively. Meanwhile, the risk of high-grade malignancy was 16.7% and 55.9% in these two categories. Disease-free survival of patients with high-grade malignancy was significantly worse than those with low- and intermediate-grade malignancy. Union combining the Milan System category [Malignant] with the presence of nodal metastasis suggested high-grade malignancy with an acceptable diagnostic sensitivity (0.889-0.963) and negative predictive value (0.900-0.966). CONCLUSIONS: The Milan System category [Malignant] with the presence of nodal metastasis suggested parotid gland tumors as high-grade malignancy in a pretreatment setting.

Impact of sarcopenia on the risk of advanced colorectal neoplasia.

BACKGROUND AND AIM: Sarcopenia is a pathological condition characterized by the progressive loss of muscle mass and increased amount of visceral fat. Recent evidence has revealed that sarcopenia is associated with certain diseases. However, the impact of sarcopenia on colorectal neoplasia has not been documented clearly. We studied the association between sarcopenia and advanced colorectal neoplasia in a large screening population. METHODS: This cross-sectional study included 14 024 asymptomatic adults who underwent first-time screening colonoscopy. Sarcopenia (class II) was defined as an appendicular skeletal muscle mass (ASM)/bodyweight (%) value more than two standard deviations below the mean for healthy young adults. ASM was estimated using bioelectrical impedance analysis. RESULTS: In a multivariable model adjusted for age, sex, obesity (body mass index ≥ 25), smoking status, alcohol intake, regular exercise, and family history of colorectal cancer, the odds ratio (OR) for advanced colorectal neoplasia on comparing participants with sarcopenia (class II) to those without sarcopenia (class I + II) was 1.52 (95% confidence interval [CI], 1.23-1.86). Further adjustment for metabolic parameters attenuated this association, but the association was still significant (OR, 1.34; 95% CI, 1.07-1.68). Furthermore, the multivariable (traditional risk factors)-adjusted OR associated with a 1% decrease on the introduction of ASM/weight% as a continuous variable in regression models was 1.04 (95% CI, 1.01-1.07) for advanced colorectal neoplasia. CONCLUSIONS: Our findings indicate that sarcopenia is significantly and progressively associated with the risk of advanced colorectal neoplasia. This association might be explained by metabolic factors that could be potential mediators of the effect of sarcopenia.

Creatinine- and cystatin C-based estimated glomerular filtration rate slopes for the prediction of kidney outcome: a comparative retrospective study.

BACKGROUND: Many studies have evaluated the usefulness of creatinine- (eGFRcr) and cystatin C-based estimated glomerular filtration rate (eGFRcys) at specific time points in predicting renal outcome. This study compared the performance of both eGFR changing slopes in identifying patients at high risk of end-stage renal disease (ESRD). METHODS: From 2012 to 2017, patients with more than three simultaneous measurements of serum creatinine and cystatin C for 1 year were identified. Rapid progression was defined as eGFR slope < - 5 mL/min/1.73 m2/year. The primary outcome was progression to ESRD. RESULTS: Overall, 1323 patients were included. The baseline eGFRcr and eGFRcys were 39 (27-48) and 38 (27-50) mL/min/1.73 m2, respectively. Over 2.9 years (range, 2.0-3.8 years) of follow-up, 134 subjects (10%) progressed to ESRD. Both the eGFRcr and eGFRcys slopes were associated with a higher risk of ESRD, independently of baseline eGFR (hazard ratio [HR] = 0.986 [0.982-0.991] and HR = 0.988 [0.983-0.993], respectively; all p <  0.001). The creatinine- and cystatin C-based rapid progressions were associated with increased risk of ESRD (HR = 2.22 [1.57-3.13], HR = 2.03 [1.44-2.86], respectively; all p <  0.001). In the subgroup analyses, the rapid progression group, defined on the basis of creatinine levels (n = 503), showed no association between the eGFRcys slope and ESRD risk (p = 0.31), whereas the eGFRcr slope contributed to further discriminating higher ESRD risk in the subjects with rapid progression based on eGFRcys slopes (n = 463; p = 0.003). CONCLUSIONS: Both eGFR slopes were associated with future ESRD risk. The eGFRcr slope was comparable with the eGFRcys slope in predicting kidney outcome.

Non-contrast liver MRI as an alternative to gadoxetic acid-enhanced MRI for liver metastasis from colorectal cancer.

BACKGROUND: Liver magnetic resonance imaging (MRI) provides reliable diagnostic performance for detecting liver metastasis but is costly and time-consuming. PURPOSE: To compare the diagnostic performance of non-contrast liver MRI to whole MRI using gadoxetic acid for detecting liver metastasis in patients with colorectal cancer (CRC). MATERIAL AND METHODS: We included 175 patients with histologically confirmed 401 liver metastases and 73 benign liver lesions. A non-contrast MRI (T1-weighted, T2-weighted, and diffusion-weighted images) with or without multidetector computed tomography (MDCT) and a whole MRI (gadoxetic acid-enhanced and non-contrast MRI) were analyzed independently by two observers to detect liver metastasis using receiver operating characteristic analysis. RESULTS: We found no significant differences in Az value (range = 0.914-0.997), sensitivity (range = 95.2-99.6%), specificity (range = 77.3-100%), or positive (range = 92.9-100%) or negative predictive value (range = 87.5-95.7%) between the non-contrast MRI with or without MDCT and the whole MRI for both observers for all lesions as well as lesions ≤1.0 cm and lesions >1.0 cm in size ( P = 0.203-1.000). Combined MDCT and non-contrast MRI led to similar numbers of false-positive diagnosis to the whole MRI (eight for Observers 1 and 4 vs. 3 for Observer 2). CONCLUSION: Non-contrast liver MRI may serve as an alternative to gadoxetic acid-enhanced MRI for detecting and characterizing liver metastasis from CRC, at least in patients with relatively high risk of liver metastasis who underwent MDCT. Non-contrast liver MRI could be beneficial especially for patients with lesions that are already documented as benign but require additional follow-up MRIs.

Natural course and prognostic factors of chronic urticaria in Korean children: A single center experience.

BACKGROUND: Chronic urticaria (CU) has an adverse effect on academic achievement and psychosocial development in children. OBJECTIVE: We aimed to investigate the natural course of CU and to identify relevant factors associated with a poor CU prognosis in Korean children. METHODS: We retrospectively analyzed 253 children with episodes of wheals or angioedema at least 3 times a week that persisted for at least 6 weeks. Clinical data and laboratory results were obtained from medical records and parental telephone interviews. Kaplan-Meier survival analysis and log rank tests were performed to assess the median time to remission of CU and prognostic factors. RESULTS: Median age at onset was 5.0 years (interquartile range, 2.5-9.1) and median follow-up period was 7.6 months (interquartile range, 3.9-19.7). Of 253 patients, 68.8% had chronic inducible urticaria and 31.2% had chronic spontaneous urticaria. Physical urticaria was the only cause of chronic inducible urticaria, and the most common physical urticaria was dermographism. Median duration to remission of CU was 10.2 months (95% confidence intervals, 8.0-12.5 months). Kaplan-Meier analysis revealed that 33.4%, 53.0%, and 71.2% of children were in remission at 6, 12, and 24 months, respectively, after the onset of CU. The presence of allergic sensitization was significantly associated with a poor CU prognosis in univariable and multivariable analyses (P=0.010 and P=0.014, respectively). CONCLUSION: Half of children with CU were in remission 10.2 months after onset. Allergic sensitization was a risk factor associated with longer duration CU.

Hepatobiliary MRI as novel selection criteria in liver transplantation for hepatocellular carcinoma.

BACKGROUND & AIMS: Hepatobiliary magnetic resonance imaging (MRI) provides additional information beyond the size and number of tumours, and may have prognostic implications. We examined whether pretransplant radiological features on MRI could be used to stratify the risk of tumour recurrence after liver transplantation (LT) for hepatocellular carcinoma (HCC). METHODS: A total of 100 patients who had received a liver transplant and who had undergone preoperative gadoxetic acid-enhanced MRI, including the hepatobiliary phase (HBP), were reviewed for tumour size, number, and morphological type (e.g. nodular, nodular with perinodular extension, or confluent multinodular), satellite nodules, non-smooth tumour margins, peritumoural enhancement in arterial phase, peritumoural hypointensity on HBP, and apparent diffusion coefficients. The primary endpoint was time to recurrence. RESULTS: In a multivariable adjusted model, the presence of satellite nodules [hazard ratio (HR) 3.07; 95% confidence interval (CI) 1.14-8.24] and peritumoural hypointensity on HBP (HR 4.53; 95% CI 1.52-13.4) were identified as independent factors associated with tumour recurrence. Having either of these radiological findings was associated with a higher tumour recurrence rate (72.5% vs. 15.4% at three years, p <0.001). When patients were stratified according to the Milan criteria, the presence of these two high-risk radiological findings was associated with a higher tumour recurrence rate in both patients transplanted within the Milan criteria (66.7% vs. 11.6% at three years, p <0.001, n = 68) and those who were transplanted outside the Milan criteria (75.5% vs. 28.6% at three years, p <0.001, n = 32). CONCLUSIONS: Radiological features on preoperative hepatobiliary MRI can stratify the risk of tumour recurrence in patients who were transplanted either within or outside the Milan criteria. Therefore, hepatobiliary MRI can be a useful way to select potential candidates for LT. LAY SUMMARY: High-risk radiological findings on preoperative hepatobiliary magnetic resonance imaging (either one of the following features: satellite nodule and peritumoural hypointensity on hepatobiliary phase) were associated with a higher tumour recurrence rate in patients transplanted either within or outside the Milan criteria.

Comprehensive Computed Tomography Radiomics Analysis of Lung Adenocarcinoma for Prognostication.

BACKGROUND: In this era of personalized medicine, there is an expanded demand for advanced imaging biomarkers that reflect the biology of the whole tumor. Therefore, we investigated a large number of computed tomography-derived radiomics features along with demographics and pathology-related variables in patients with lung adenocarcinoma, correlating them with overall survival. MATERIALS AND METHODS: Three hundred thirty-nine patients who underwent operation for lung adenocarcinoma were included. Analysis was performed using 161 radiomics features, demographic, and pathologic variables and correlated each with patient survival. Prognostic performance for survival was compared among three models: (a) using only clinicopathological data; (b) using only selected radiomics features; and (c) using both clinicopathological data and selected radiomics features. RESULTS: At multivariate analysis, age, pN, tumor size, type of operation, histologic grade, maximum value of the outer 1/3 of the tumor, and size zone variance were statistically significant variables. In particular, maximum value of outer 1/3 of the tumor reflected tumor microenvironment, and size zone variance represented intratumor heterogeneity. Integration of 31 selected radiomics features with clinicopathological variables led to better discrimination performance. CONCLUSION: Radiomics approach in lung adenocarcinoma enables utilization of the full potential of medical imaging and has potential to improve prognosis assessment in clinical oncology. IMPLICATIONS FOR PRACTICE: Two radiomics features were prognostic for lung cancer survival at multivariate analysis: (a) maximum value of the outer one third of the tumor reflects the tumor microenvironment and (b) size zone variance represents the intratumor heterogeneity. Therefore, a radiomics approach in lung adenocarcinoma enables utilization of the full potential of medical imaging and could play a larger role in clinical oncology.

Factors Associated With Host Immune Response and Number of Lymph Nodes: A Large Retrospective Cohort Study.

BACKGROUND: The host immune response (HIR) against tumor cells is one of the key players in antitumor activities. However, the relationship between HIR and regional lymph nodes (LN) and their impacts on prognosis have not been studied. METHODS: This study analyzed HIR and clinicopathologic factors for 8819 consecutive gastric cancer patients who underwent gastrectomy and D2 LN dissection. The findings confirmed Epstein-Barr virus (EBV) with Epstein-Barr encoding region in situ hybridization, HIR grading (G1, G2, and G3), LN numbers classified into seven groups, and performed ordinal regression analysis. RESULTS: The mean number of LNs was 41. A higher degree of HIR was significantly associated with male sex, EBV+, non-intestinal histology by Lauren classification, earlier American Joint Committee on Cancer (AJCC) stage, and greater number of LNs (P < 0.001). Female gender, younger age (< 60 years), EBV+, non-intestinal histology, higher HIR grade (G2 and G3), larger tumor size, and deeper invasion depth were significantly related to a higher number of LNs, with an odds ratio greater than 1. In cancer-specific survival analyses, EBV+, younger age, higher HIR grade (G3), and increased number of LNs were independent prognostic factors in addition to AJCC stage. CONCLUSIONS: The HIR was associated with increased number of LNs was a significant favorable prognosticator.

Optimal cutoff of pretreatment neutrophil-to-lymphocyte ratio in head and neck cancer patients: a meta-analysis and validation study.

BACKGROUND: The prognostic role of neutrophil-to-lymphocyte ratio (NLR) has been proposed in head and neck squamous cell carcinoma (HNSCC). However, it is currently unclear which cutoff values of NLR could consistently and independently differentiate HNSCC patients to better and worse prognosis groups. METHODS: We performed a meta-analysis of prognostic significance of pretreatment NLR values, using data extracted from 24 relevant articles. Main outcomes were overall survival (OS) and disease-free survival (DFS) in HNSCC patients. Pooled hazard ratio (HR) and 95% confidence intervals (95%CI) were calculated using the random effect model for outcomes. Impacts of NLR cutoff values across the studies were assessed with a meta-regression analysis. Results were validated using an independent data set of patients (n = 540). RESULTS: Pretreatment high NLR values above the cutoff were significantly associated with shorter OS (HR = 1.96, 95%CI = 1.66-2.31) and DFS (HR = 1.90, 95%CI = 1.41-2.54). Of note, NLR cutoffs ranging from 1.9 to 6.0 did not affect HR of OS or DFS in meta-regression analyses. In an independent cohort, any NLR cutoff between 2 and 6 produced significant HR of OS, similarly. Instead of binary cutoffs, three subgroups of NLR (< 2, 2 to 6, and ≥ 6) showed significant differences of OS in survival analyses. CONCLUSIONS: Meta-analyses confirmed that pretreatment NLR values above the cutoff were associated with shorter survival in HNSCC patients. However, the binary cutoffs of NLR values were variable across studies. Rather, pretreatment NLR values below 2 and above 6 using a three-tier classification (< 2, 2 to 6, and ≥ 6) could consistently imply better and worse prognosis in HNSCC patients, which could be readily translated to clinics.

Hepatic neuroendocrine tumour: Apparent diffusion coefficient as a potential marker of prognosis associated with tumour grade and overall survival.

OBJECTIVES: To evaluate the correlation between grade of hepatic neuroendocrine tumours (NETs) according to the 2010 World Health Organization (WHO) classification and the apparent diffusion coefficient (ADC) and to assess whether ADC value can predict overall survival (OS) after diagnosis of hepatic NETs. METHODS: The study included 63 patients who underwent magnetic resonance (MR) imaging with diffusion-weighted images for the evaluation of hepatic NETs. The correlation between qualitative and quantitative MR imaging findings, including ADC values, and WHO classifications was assessed. The association between ADC value and OS was analyzed. RESULTS: The ADC values and WHO classification of hepatic NETs were moderately negatively correlated in a statistically significant manner (ρ = -0.57, p < 0.001). The OS rates were significantly different according to the ADC value (low ADC vs. high ADC, p = 0.006) as well as WHO classifications (G1+ G2 vs. G3, p = 0.038). However, multivariate analysis revealed that the only independent predictor for OS was a low ADC value (hazard ratio: 3.37, p = 0.010). CONCLUSION: There was a significant correlation between the ADC value of hepatic NETs and the WHO tumour grade. Additionally, the ADC value of a hepatic NET might be more accurate than the current WHO tumour grade for predicting OS. KEY POINTS: • ADC values of hepatic NET and WHO tumour grade were negatively correlated. • Lower ADC values of hepatic NET were significantly correlated with worse OS. • ADC value might be more accurate than WHO grade for predicting OS.

Clinical usefulness of capnographic monitoring when inserting a feeding tube in critically ill patients: retrospective cohort study.

BACKGROUND: It is not rare for a small-bore feeding tube to be inserted incorrectly into the respiratory system in critically ill patients. Thus, monitoring is necessary to prevent respiratory malplacement of the tube. We investigated the utility of capnographic monitoring to prevent respiratory complications due to feeding tube mispositioning in critically ill patients. METHODS: This study was a pre and post-interventional study, including 445 feeding tube placements events studied retrospectively in the medical and surgical intensive care units of the Samsung Medical Center. We compared outcomes between time periods before and after capnographic monitoring and documented any respiratory complications. RESULTS: Feeding tubes were inserted in 275 cases without capnographic monitoring. Capnographic monitoring was performed in 170 cases. Sixteen patients (4%) had respiratory complications of all tube placements. Feeding tube was inserted into the trachea in 11 (2%) patients and for a pneumothorax in five (1%) patients. Fourteen cases of respiratory complications were detected in the control group (14/275, 5%, 10 tracheal insertions and four pneumothoraxes). Two respiratory complications were detected in the capnographic monitoring group (2/170, 1%, one tracheal insertion and one pneumothorax). Respiratory complications were detected less frequently in the capnographic monitoring group than that in the control group (P = 0.035). CONCLUSIONS: Capnographic monitoring is simple, easy to learn, and may be useful to prevent respiratory complications when placing a feeding tube in a critically ill patient.

Integrated copy number and gene expression profiling analysis of Epstein-Barr virus-positive diffuse large B-cell lymphoma.

Viral oncogenes and host immunosenescence have been suggested as causes of Epstein-Barr virus-positive diffuse large B-cell lymphoma (EBV + DLBCL) of the elderly. To investigate the molecular genetic basis of immune evasion and tumor outgrowth, we analyzed copy number alterations (CNAs) and gene expression profiles in EBV + DLBCL samples compared with EBV - DLBCL. There were relatively few genomic alterations in EBV + DLBCL compared with those detected in EBV-negative DLBCL. The most frequent CNAs (>30%) in EBV + DLBCLs were gains at 1q23.2-23.3, 1q23.3, 1q32.1, 5p15.3, 8q22.3, 8q24.1-24.2, and 9p24.1; losses at 6q27, 7q11.2, and 7q36.2-36.3 were also recurrent. A gene expression profile analysis identified the host immune response as a key molecular signature in EBV + DLBCL. Antiviral response genes, proinflammatory cytokines, and chemokines associated with the innate immune response were overexpressed, indicating the presence of a virusinduced inflammatory microenvironment. Genes associated with the B-cell receptor signaling pathway were downregulated. An integrated analysis indicated that SLAMF1 and PDL2 were key targets of the gains detected at 1q23.2-23.3 and 9p24.1. The chromosomal gain at 9p24.1 was associated with poor overall survival. Taken together, our results led to the identification of recurrent copy number alterations and distinct gene expression associated with the host immune response in EBV + DLBCL. We suggest that the upregulation of PDL2 on 9p24.1 promotes immune evasion and is associated with poor prognosis in EBV + DLBCL.